The present invention relates to treatment of symptoms of chronic pelvic pain syndromes generally inclusive of syndromes such as prostatis.
Prostatitis and prostatodynia are extremely prevalent diseases in men (Collins M M, et al., “How common is prostatitis? A national survey of physician visits,” Journal of Urology, 159:1224–1228 (1998)). There are more outpatient visits for prostatitis than for benign prostatic hypertrophy (BPH) or prostate cancer. Although the epidemiologic evidence is limited, it appears that the prevalence of prostatitis is approximately 2–9% in adult men. It has been suggested that 35–50% of men are affected by prostatitis at some time in life. Based on the National Ambulatory Medical Care Surveys from 1990–1994, approximately 2 million ambulatory visits are made annually for prostatitis. This accounts for 8% of all visits to urologists and 1% of all visits to primary care physicians. Many men remain symptomatic for much of their lives.
Chronic pelvic pain syndrome encompasses a variety of related syndromes including prostatitis and can be characterized by evidence of prostatic inflammation and by the presence or absence of white blood cells in prostatic fluid and/or pain associated with the prostate. This inflammation of the prostate causes pain in the abdomen, testicles, or tip of the penis, urination problems, and painful ejaculation. Its cause often cannot be determined. Bacteria are usually not detected in the urine. Fever, chills, or other signs of an infection are not present. Within this group of syndromes, the origins of chronic idiopathic prostatitis, asymptomatic prostatitis, and prostatodynia are problematic and are probably the least understood. The origin of these diseases has been attributed to some undefinable bacterial or viral infection, but this has never been proven. These syndromes do not exist prior to puberty but have a peak incidence between the ages of 18 and 50. It is possible that these three specific entities actually represent the same disease process in different phases or forms. Suggestions as to the origins of these conditions have included a chemical imbalance in the prostate, infection undetected by current microbiological methods, and autoimmunity to the prostate gland itself.
The causes of noninflammatory chronic pelvic pain syndrome may be the same as those for inflammatory chronic pelvic pain syndrome. Some doctors think that the prostate may not be involved at all but that a combination of things, including nervous system problems, strained pelvic floor muscles, and emotional factors cause the pain.
Chronic nonbacterial prostatitis is an inflammatory and pain condition of unknown etiology characterized by excessive inflammatory cells in prostatic secretions despite no history of documented urinary tract infection and negative bacterial cultures of urine and prostatic secretions. Chronic nonbacterial prostatitis is even more common than bacterial prostatitis. Symptoms simulate those of chronic bacterial prostatitis and these patients usually show an increase in the number of white blood cells and oval fat bodies in their expressed prostatic secretions. However, they rarely have a history of urinary tract infection, and lower-tract localization cultures fail to reveal a pathogenic organism. Patients with prostatodynia have negative bacterial cultures, normal prostatic secretions, and no history of urinary tract infection. Symptoms of chronic nonbacterial prostatitis and prostatodynia vary but include urinary urgency and frequency, nocturia, dysuria, and pain and discomfort perceived in the pelvic, suprapubic, or genital area. Sometimes postejaculatory pain and discomfort are prominent features. Physical findings for both conditions are nonspecific.
This condition has recently been reclassified into two major subtypes, inflammatory chronic pelvic pain syndrome (CPIIIA presence of leucocytes in the post-prostate massage urine sample); and non-inflammatory chronic pelvic pain syndrome (CPIIIB formerly termed prostatodynia) a painful prostate in which no infection or inflammation is present.
The etiology of the condition has, to date, not been fully elucidated. Research has focused on finding sub-clinical relationships to several infectious disease pathogens as well as non-infectious disease entities such as neuromuscular dysfunction of the bladder neck or uro-genital diaphragm, allergies, psychological, and autoimmune vectors. To date therapeutic approaches to this condition remains, for the most part, ineffective.
Chronic pelvic pain syndrome which represents about 90% of men with prostatis is distinguished from those caused by bacterial infection which include acute bacterial prostatitis (also known as Category I prostatitis) which is a serious infection in the prostate and which causes severe symptoms. Acute bacterial prostatitis is treatable by antibiotics, pain and fever medication, stool softeners, fluids and rest.
Chronic pelvic pain syndrome is also distinguished from chronic bacterial prostatitis (also known as Category II prostatis) which represents a more resistant infection requiring longer term therapy can occur more often in men who have had repeated urinary tract infections. Infected prostatic caleuli (stones) can make the infection more difficult to cure and may require surgical removal. Surgery may also be required if urinary tract problems such as narrowing of the bladder neck or urethra are causing the problems.
Noninflammatory chronic pelvic pain is extremely difficult to treat because its cause is unknown. The primary goal of treatment is to relieve symptoms. Non-narcotic pain medications, muscle relaxers, and alpha-blockers are used. Physical therapy, medications to reduce anxiety, exercise, massage therapy, biofeedback, or stress reduction may help some men. Home treatment may also be helpful in relieving the symptoms.
Of interest to the present invention is the disclosure of Guess et al., U.S. Pat. No. 6,054,455 which is directed to methods for treatment or prevention of chronic nonbacterial prostatitis and prostadyria by administration of tachykinin receptor antagonist is a neurokinin-1 receptor antagonist. Also of interest is the disclosure of Gormley, et al., U.S. Pat. No. 5,629,318 which is directed to a method for treatment of chronic prostatitis with 17.beta.-N-monosubstituted-carbamoyl-4-aza-5.alpha.-androst-1-en-3-one compounds such as testosterone-5.alpha.-reductase inhibitors for the treatment of chronic prostatitis. Despite these and other treatments for chronic pelvic pain syndromes there remains a need in the art for improved treatment methods.
Nevertheless, there are currently no established treatments for chronic nonbacterial prostatitis or prostatodynia. Antibiotics are often prescribed empirically, but with little evidence of efficacy. Alpha blockers are sometimes prescribed for prostatodynia, but their efficacy has not been established. Patients who respond poorly to medical management or have significant emotional problems are referred for psychiatric intervention. Hot sitz baths and anticholinergic drugs are generally employed to provide some symptomatic relief, as is periodic prostatic massage. Accordingly, there remains a need in the art for improved methods for treatment of chronic pelvic pain syndromes.
Of interest to the present invention is the disclosure of McMichael, U.S. Pat. No. 4,692,332 which relates to the use of equine chorionic gonadotropin and human chorionic gonadotropin (hCG) in combination with an immune enhancer such as a lysate of Staphylococcus aureus for treatment of malignant neoplasia. The mechanism of action in the treatment of the cancer was proposed to involve chorionic gonadotropin as a signal molecule capable of inducing apoptosis via membrane changes on the transformed cell at the molecular level, or alternatively by altering the electrical charge of the transformed cell to render it more susceptible to immune elimination. This patent further taught the need to stimulate the cell mediated immune response so that necrotic debris associated with tumor reduction could be efficiently phagocytized to prevent a potentially fatal Herxheimer-type reaction. U.S. Pat. No. 4,692,332, however, fails to disclose the use of chorionic gonadotropin for treatment of non-neoplastic states such as benign prostatic hypertrophy.
Also of interest to the present invention is the disclosure of McMichael, U.S. Pat. No. 5,610,136 which discloses methods of treating benign prostatic hypertrophy by administration of a chorionic gonadotropin or a pharmaceutically active fragment or derivative thereof. hCG, a signaling molecule, is thought to induce apoptosis (cellular death) via membrane changes and down regulation of the BCL2 at the genomic level rendering the cell susceptible to apoptosis. This may be likened to a negative feedback signal and be similar to cutaneous immunization for allergic reactions. At optimal concentrations hCG reduces the tendency for uncontrolled cell proliferation which occurs in abnormal accelerated cellular-growth conditions such as benign prostatitic hypertrophy (BPH).